Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka.
Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
Lab Med. 2022 May 5;53(3):e48-e50. doi: 10.1093/labmed/lmab083.
Fumaric aciduria resulting from fumarate hydratase deficiency is a rare inherited disorder of the Krebs tricarboxylic acid cycle that is characterized by neurologic manifestations, a spectrum of brain abnormalities, and the excretion of fumaric acid in urine. We describe a 3 year old Sri Lankan boy who was referred at age 10 months with poor weight gain and hypotonia for further laboratory investigations. In addition to global developmental delay, there were noticeable dysmorphic features with a prominent forehead, low-set ears, micrognathia, and hypertelorism with persistent neutropenia. Urine organic acid assay revealed a massive elevation of fumaric acid on 2 occasions. Molecular analysis revealed a homozygous likely pathogenic missense variant, NM000143.3:c.1048C>T p. (Arg350Trp), in the FH gene, confirming the biochemical diagnosis. Our patient was the first patient in Sri Lanka molecularly diagnosed with fumaric aciduria. This case study highlights the importance of performing organic acid assays in children presenting with neurologic manifestations especially when these are suspected to have a metabolic basis.
延胡索酸尿症是一种罕见的三羧酸循环遗传疾病，由延胡索酸水合酶缺乏引起，其特征为神经表现、一系列脑异常和尿中排出延胡索酸。我们描述了一名 3 岁的斯里兰卡男孩，他在 10 个月大时因体重增长不良和低张力被转介进行进一步的实验室检查。除了全面发育迟缓外，还存在明显的畸形特征，包括额突出、低位耳、小颌畸形和宽眼距，且持续存在中性粒细胞减少症。两次尿液有机酸测定均显示大量延胡索酸升高。分子分析显示 FH 基因中存在纯合的可能致病性错义变异，NM000143.3:c.1048C>T p.(Arg350Trp)，证实了生化诊断。我们的患者是斯里兰卡首例分子诊断为延胡索酸尿症的患者。该病例研究强调了在出现神经表现的儿童中进行有机酸测定的重要性，特别是当这些表现疑似为代谢性疾病时。
